The physiology of platelet secretion has many features in common with the secretory physiology of endocrine and neuronal cells; and a number of the biogenic amines synthesized, stored, and secreted by these different cell types are similar. Platelet membrane glycoproteins (GP) appear to be major factors determining cell-cell recognition, adhesion and secretion. We have discovered a new mechanism of platelet activation by small cross-linking reagents that is independent of Ca and fibrinogen. The most potent compound, a disulfonic acid stilbene (DIDS), with a 12 Ao span, reacts with platelet membrane proteins of molecular weights 52, 170, and 230 kD, possibly involving glycoprotein Ib, a major adhesion protein of platelets. Suramin, a drug used in experimental treatment of AIDS and malignancies was found to inhibit the active site of thrombin, to inhibit thrombin-induced platelet activation, and to cause variations in the thrombin time and, increases in platelet aggregability as much as 20-fold normal. In patients with microvascular angina, we found no evidence to support abnormal platelet responsiveness to standard agonists. Two patients with congenital microthrombocytopenia of a degree similar to that of Wiscott-Aldrich syndrome (WAS) were found to have shortened platelet survival but normal immunologic assessments, electron micrograph of platelets, and membrane glycoproteins. They appear to represent an, as yet, undescribed syndrome differing from WAS. Newly recognized mucosal peptide antimicrobials, maganins and uteroglobulin (UG) were found to inhibit platelet aggregation by preventing the fibrinogen-receptor interaction without affecting platelet secretion. One hydrolytic 4 peptide fraction of UG most active, the intact UG least active. Platelet survival in ITP utilizing 111 in indicated that platelet destruction, not decreased production accounts for development of ITP.